Brahmi Mostapha, Adli Djallal Eddine H, Kaoudj Imane, Alkholifi Faisal K, Arabi Wafaa, Sohbi Soumia, Ziani Kaddour, Kahloula Khaled, Slimani Miloud, Sweilam Sherouk Hussein
Department of Biological Science, Faculty of Natural and Life Sciences, University of Ahmed Zabana, Relizane 48000, Algeria.
Laboratory of Biotoxicology, Pharmacognosy and Biological Valorization of Plants (LBPVBP), Department of Biology, Faculty of Sciences, University of Dr MoulayTahar, Saida 20000, Algeria.
Plants (Basel). 2025 Jan 4;14(1):130. doi: 10.3390/plants14010130.
The aim of our research was to understand the impact of ochratoxin A (OTA) exposure on various physiological and behavioral aspects in adult Wistar rats, and to evaluate the efficacy of a essential oil (EOC) treatment in restoring the damage caused by this toxin. The essential oils were extracted by hydrodistillation, a yield of 12.70% was obtained for EOC, and the GC-MS characterization of this essential oil revealed that its principal major components are eugenol (80.95%), eugenyl acetate (10.48%), β-caryophyllene (7.21%), and α-humulene (0.87%). Acute OTA intoxication was induced by an intraperitoneal (IP) injection of 289 µg/kg/b.w. every 48 h for 12 doses, resulting in significant reductions in the body and brain weights of exposed rats when compared with controls. The neurobehavioral analysis using several behavioral testing techniques, such as the forced swimming, the dark/light test, the Morris water maze, and the open field test, clearly revealed that OTA exposure causes neurobehavioral disorders, including decreased locomotor activity, a reduced willingness to explore the environment, reflecting a state of stress, anxiety and depression, as well as impaired memory and learning. In addition, OTA intoxication has been associated with metabolic disturbances such as hyperglycemia and hypercortisolemia. However, treatment with EOC mitigated these adverse effects by improving body and brain weights and restoring neurobehavioral function. The in silico analysis revealed significant affinities between clove oils and two tested esterase enzymes (ACh and BuChE) that were more than or similar to the four neurotransmitters "dopamine, serotonin, norepinephrine, and glutamic acid" and the co-crystallized ligands NAG, MES, and GZ5. These results highlight the therapeutic potential of EOC in combating the toxic effects of OTA and pave the way for future research into the mechanisms of action and therapeutic applications of natural compounds in the prevention and treatment of poison-induced diseases.
我们研究的目的是了解赭曲霉毒素A（OTA）暴露对成年Wistar大鼠各种生理和行为方面的影响，并评估一种香精油（EOC）治疗对恢复该毒素所造成损害的效果。香精油通过水蒸馏法提取，EOC的得率为12.70%，该香精油的气相色谱-质谱表征显示其主要成分是丁香酚（80.95%）、乙酸丁香酯（10.48%）、β-石竹烯（7.21%）和α-葎草烯（0.87%）。通过每48小时腹腔注射289μg/kg体重，共注射12剂来诱导急性OTA中毒，与对照组相比，暴露大鼠的体重和脑重显著降低。使用几种行为测试技术进行神经行为分析，如强迫游泳、明暗试验、莫里斯水迷宫和旷场试验，清楚地表明OTA暴露会导致神经行为障碍，包括运动活动减少、探索环境的意愿降低，反映出应激、焦虑和抑郁状态，以及记忆和学习受损。此外，OTA中毒与高血糖和高皮质醇血症等代谢紊乱有关。然而，EOC治疗通过改善体重和脑重以及恢复神经行为功能减轻了这些不良反应。计算机模拟分析显示丁香精油与两种测试的酯酶（乙酰胆碱酯酶和丁酰胆碱酯酶）之间有显著亲和力，这些亲和力大于或类似于四种神经递质“多巴胺、血清素、去甲肾上腺素和谷氨酸”以及共结晶配体N-乙酰葡糖胺、甲磺酸酯和GZ5。这些结果突出了EOC在对抗OTA毒性作用方面的治疗潜力，并为未来研究天然化合物在预防和治疗中毒性疾病中的作用机制和治疗应用铺平了道路。
